Our previous studies suggested that the relative resistance of young gerbils may be attributed to neuronal function. On the other hand reports implicated of heat shock protein HSP27 to play a protective role against neuronal injury. To elucidate further, the mechanisms responsible for the observed age dependent susceptibility to brain ischemia, we investigated the effect of ischemia on HSP 72 expression, a transcriptional and translational level in the hippocampus of young and adult gerbils. The HSP in RNA expression was observed in all hippocampal areas within 3 hours of reflow, reaching the maximum by 8 hours of reflow in both young and adult gerbils. However, a much stronger in situ hybridization was observed at 1 hour of reperfusion in the hippocampus of young than that seen in adult animals. A progressive decrease in HSP 72 mRNA expression was seen in various areas of hippocampus except CA1. At 48 hours, the persisting expressions of mRNA in CA1 was more marked in young than adult gerbils. The appearance of HSP 72 protein was detected at a later time than that observed for mRNA. The most striking difference was seen in CA1 neurons which showed a more marked accumulation of HSP 72 protein in young than that observed in adult animals. Present experiments evaluated mRNA expression of constitutive heat shock 72 (HSC 72) protein and survival of hippocampal CA1 neurons. The data indicate a similar pattern of HSC 72 mRNA expression as that seen for HSP 72 mRNA in young and adult gerbils. The more marked accumulation of HSP protein is associated with greater survival of hippocampal CA1 neurons in young than adult. These findings support our previous postulation that endogenous tolerance of immature neurons may be related to higher transcriptional activity.